核糖核酸
转移RNA
癌变
癌症
生物
癌症研究
磷酸化
恶性肿瘤
分子生物学
化学
细胞生物学
遗传学
基因
作者
Xiaoling Ying,Wenyu Hu,Yapeng Huang,Yifan Lv,Ding Ji,Cong Chen,Baotong Yang,Chengcheng Zhang,Yaomin Liang,Haiqing Zhang,Mingrui Liu,Gang Yuan,Wenqi Wu,Weidong Ji
标识
DOI:10.1002/advs.202400115
摘要
Abstract Emerging evidence indicates that transfer RNA (tRNA)‐derived small RNAs (tsRNAs), originated from tRNA with high abundance RNA modifications, play an important role in many complex physiological and pathological processes. However, the biological functions and regulatory mechanisms of modified tsRNAs in cancer remain poorly understood. Here, it is screened for and confirmed the presence of a novel m 7 G‐modified tsRNA, m 7 G‐3′‐tiRNA Lys TTT (mtiRL), in a variety of chemical carcinogenesis models by combining small RNA sequencing with an m 7 G small RNA‐modified chip. Moreover, it is found that mtiRL, catalyzed by the tRNA m 7 G‐modifying enzyme mettl1, promotes bladder cancer (BC) malignancy in vitro and in vivo. Mechanistically, mtiRL is found to specifically bind the oncoprotein Annexin A2 (ANXA2) to promote its Tyr24 phosphorylation by enhancing the interactions between ANXA2 and Yes proto‐oncogene 1 (Yes1), leading to ANXA2 activation and increased p‐ANXA2‐Y24 nuclear localization in BC cells. Together, these findings define a critical role for mtiRL and suggest that targeting this novel m 7 G‐modified tsRNA can be an efficient way for to treat BC.
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